This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 1. The enodthelium is a vital component of the vascular system and it has been documented that it plays a vital roel in the control of cardiovascular risk factors (1). Phosphodistrerase type 5(PDE 5)substances have been shown that by inactivating cyclic guanosine phosphates (cGMP), they increase the availability of NO produced by the endothelial sytem (2,3). 2. We have developed a simple non-invasive test (acetylcholine ionyophoresis - ACH Iph), identifying the status of the endothelial system. BY applying this methodolgy to normal subjects as wells as to patients with peripheral arterial disease, diabetes, hypertensive disease and hypercholesterolemia, we will be able to determine if PDE 5 medication, given to the described groups of subjects, will improve their endothelial activity. In the positive case it will represent a significant improvement of patient's cardiovascualr risk factors.